| Objective (s):This study is about the expression of NK cell activation receptor NKG2D, MHC class I molecules and related cytokines IL-10, IL-15, IFN-y levels in liver tissues of patients with primary biliary cirrhosis, and analyzed the correlation between these indexes and intrahepatic inflammation.To explore the Monocytes regulate NK cell by the NKG2D/MICA and cytokine pathways in primary biliary cirrhosis.Methods:Collected 30 patients with primary biliary cirrhosis in the Second Affiliated Hospital of Kunming Medical University, Department of internal medicine treatment at 2014 August to 2015 June. The age range was 18 to 76 years old, the average age was 47.2+13.53 years old,8 cases of male,22 cases of female. At the same time, collected 15 patients with CHB and 10 patients with NAFLD as the control group. In CHB group. The age range was 26 to 65 years old, the average age was 42.46+11.36 years old,10 cases of male,5 cases of female.In NAFLD group, The age range was 25 to 56 years old, the average age was 43.5+10.55 years old,8 cases of male,2 cases of female. The expression of NKG2D, MICA, IFN-y, IL-10 and IL-15 were observed in the liver tissues in three group by immunohistochemistry method.,to judge the degree of liver inflammation and fibrosis in liver tissues by pathological grading and staging of chronic hepatitis in China,and analyze the relationship between the expression of cytokines and inflammation in the liver.The relevant test data were statistically analyzed with SPSS 19.0 software package,the comparison between the two groups using t test.Spearman rank analysis was used to analysis the correlation between the expression of NKG2D,MlCA,IFN-y,IL-10,IL-15 and liver function.Results:1.PBC, CHB, NAFLD group of liver inflammation:(1) PBC group:5 cases of G1,6 cases of G2,10 cases of G3,9 cases of G4; 10 cases of S3,9 cases of S4.(2) CHB group:5 cases of G1,7 cases of G2,3 cases of G3; 6 cases of S1,7 cases of S2,2 cases of S3.(3) NAFLD group:4 cases of G1,4 cases of G2,2 cases of G3; 5 cases of S1,2 cases of S2,2 cases of S3,1 cases Of S4.2.PBC, CHB, NAFLD group immunohistochemical results:(1) The expression of NKG2D:NKG2D expression on NK cells, was expressed in the nucleus and cytoplasm, mainly in cytoplasm.Compared with the group of NAFLD and CHB, the expression of NKG2D was increased in PBC group.In PBC group, G3-4 compared with the G1-2,the expression of NKG2D showed a rising trend, the difference is statistically significant (G1-2 vs. G3-4,t=-1.46,p=0.004).In PBC group, with the increase of the degree of fibrosis, the expression of NKG2D was decreased,the difference has statistical significance(S3 vs. S4,t=-1.52,P=0.02).The expression of NKG2D was negative in CHB group and NAFLD group.(2)The expression of MICA:in PBC group, MICA is mainly expressed in the cytoplasm of macrophages. In PBC group,the expression of MICA was negative in G1-2,but the G3-4 was expressed. With the increase of the degree of inflammation, the expression of MICA showed a rising trend, the difference was not statistically significant(t=-2.20,P> 0.05). In PBC group, with the increased of degree of fibrosis, MICA expression showed rising trend, the difference was not statistically significant (t=-2.64,p>0.05). The expression of MICA was negative in CHB group and NAFLD group.(3) The expression of IL-15:PBC group and CHB group can be observed that IL-15 is mainly expressed on macrophages, in the nucleus and cytoplasm are expressed, but mainly in the cytoplasmic expression. The expression level of IL-15 in PBC group compared with the CHB group, the difference was not statistically significant (t=-1.424,p>0.05;t=-1.64,p>0.05).In CHB and PBC group, G3-4 compared with the G1-2, IL-15 expression showed a rising trend, but there were no statistical significance (t=-1.598,p>0.05;t=-1.19,p>0.05).In PBC and CHB group, with the increase of the degree of fibrosis, IL-15 expression has rise trend, but the difference was not statistically significant (t=-1.62,p>0.05;t=-1.54,p>0.05) NAFLD group was negative expression of IL-15.(4) The expression of IL-10:PBC group and CHB group can be observed that IL-10 is mainly expressed on macrophages, in the nucleus and cytoplasm are expressed, mainly in the cytoplasmic expression. In PBC group and CHB group, G3-4 levels were negative expression of IL-10. In PBC group,only G1 expression of IL-10.In CHB group, Gland G2 both expressed IL-10, and the expression level of G2 was lower than that of G1, suggesting that with the increase of the degree of inflammation, the expression of IL-10 was reduced, even negative expression.In CHB group, with the increase of the degree of fibrosis, IL-10 expression was decreased, the difference was not statistically significant(t=-1.522,p>0.05) NAFLD group was negative expression of IL-10.(5)The expression of IFN-y:the three groups of IFN-gamma were negative expression in this experiment.3.The correlation between the IL-15、NKG2D、MICA、IL-10、IFN-γand liver function analysis of in patients with PBC.(1)The expression level of IL-15 was positively correlated with ALP (r=0.241, P= 0.014); the expression level of IL-15 was positively correlated with GGT(r= 0.407, P= 0.045). It suggests that the expression of IL-15 is related to the development of PBC, which may be a certain role in the injury of hepatic cells and bile duct epithelial cells in PBC patients.(2) NKG2D, MICA, IL-10 expression was not correlated with liver function (p>0.05).(3) There was no correlation between the expression of IL-15, NKG2D, MICA and IL-10(p>0.05).(4) The expression of IFN-was negative in patients with PBC.Conclusion(s):1.with the increase of the degree of inflammation, the expression of NKG2D was up-regulated, and the expression of NKG2D decreased with the increase of the degree of fibrosis, suggesting that the NK cells were activated and induced liver injury in the early stage of PBC, but NK cell activation was inhibited in the late stage of PBC.2. In primary biliary cirrhosis(PBC) group, MICA expression on monocytes was increased, and NK cells high expression the activating receptor NKG2D, suggesting that monocytes may regulated the function of NK cells by the NKLG2D/MICA pathway and participate in the pathogenesis of PBC.3. In PBC group, the expression of MICA on monocytes was significantly decreased compared with the expression of NKG2D on NK cells, suggesting that there are other factors affect the activation of NKG2D.4 Abnomal secretion of cytokine is involved in the pathogenesis of PBC.5 The expression of IL-15 is related to the development of PBC, which may be an auxiliary diagnostic index of PBC. |
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